Molecular pathology underlying the robustness of cancer stem cells

Autor: Hideyuki Saya, Go J. Yoshida
Rok vydání: 2021
Předmět:
0301 basic medicine
Medicine (General)
Prrx1
Paired-related homeodomain transcription factor 1

GSH
reduced glutathione

medicine.medical_treatment
Intratumoral heterogeneity
Review
ALDH
Aldehyde dehydrogenase

Targeted therapy
0302 clinical medicine
NSCLC
non–small cell lung cancer

IL
Interleukin

HNSCC
Head and neck squamous cell cancer

CTC
Circulating tumor cell

Molecular pathology
E/M
Epithelial/mesenchymal

ABC
ATP-binding cassette

DTC
Disseminated tumor cell

Nrf2
nuclear factor erythroid 2–related factor 2

OXPHOS
Oxidative phosphorylation

CD44 variant
Phenotype
MET
mesenchymal-to-epithelial transition

EGF
Epidermal growth factor

TGF-β
Transforming growth factor–β

EMT
Epithelial-to-mesenchymal transition

Plasticity
Epithelial-to-mesenchymal transition (EMT)
Biomedical Engineering
CD44v
CD44 variant

CSC
Cancer stem cell

Biology
Biomaterials
03 medical and health sciences
R5-920
ECM
Extracellular matrix

Cancer stem cell
Niche
medicine
Progenitor cell
BMP
Bone morphogenetic protein

GSC
Glioma stem cell

Tumor microenvironment
QH573-671
EpCAM
Epithelial cell adhesion moleculeE

CAF
Cancer-associated fibroblast

Robustness (evolution)
HGF
Hepatocyte growth factor

Radiation therapy
030104 developmental biology
Cancer research
SRP1
Epithelial splicing regulatory protein 1

Cytology
CagA
Cytotoxin-associated gene A

030217 neurology & neurosurgery
MAPK
mitogen-activated protein kinase

Developmental Biology
ROS
Reactive oxygen species
Zdroj: Regenerative Therapy
Regenerative Therapy, Vol 17, Iss, Pp 38-50 (2021)
ISSN: 2352-3204
Popis: Intratumoral heterogeneity is tightly associated with the failure of anticancer treatment modalities including conventional chemotherapy, radiation therapy, and molecularly targeted therapy. Such heterogeneity is generated in an evolutionary manner not only as a result of genetic alterations but also by the presence of cancer stem cells (CSCs). CSCs are proposed to exist at the top of a tumor cell hierarchy and are undifferentiated tumor cells that manifest enhanced tumorigenic and metastatic potential, self-renewal capacity, and therapeutic resistance. Properties that contribute to the robustness of CSCs include the abilities to withstand redox stress, to rapidly repair damaged DNA, to adapt to a hyperinflammatory or hyponutritious tumor microenvironment, and to expel anticancer drugs by the action of ATP-binding cassette transporters as well as plasticity with regard to the transition between dormant CSC and transit-amplifying progenitor cell phenotypes. In addition, CSCs manifest the phenomenon of metabolic reprogramming, which is essential for maintenance of their self-renewal potential and their ability to adapt to changes in the tumor microenvironment. Elucidation of the molecular underpinnings of these biological features of CSCs is key to the development of novel anticancer therapies. In this review, we highlight the pathological relevance of CSCs in terms of their hallmarks and identification, the properties of their niche—both in primary tumors and at potential sites of metastasis—and their resistance to oxidative stress dependent on system xc (−).
Highlights • Intratumoral heterogeneity driven by CSCs is responsible for therapeutic resistance. • CTCs survive in the distant organs and achieve colonization, causing metastasis. • E/M hybrid cancer cells due to partial EMT exhibit the highest metastatic potential. • The CSC niche regulates stemness in metastatic disease as well as in primary tumor. • Activation of system xc(-) by CD44 variant in CSCs is a promising therapeutic target.
Databáze: OpenAIRE